Liposomes containing oligonucleotides

Abstract

It is possible to radiosensitize tumor cells by administration of compositions containing the Human antisense c-raf- 1 oligodeoxyribonucleotide (ODN/oligo) sequence: 5 ′-GTGCTCCATTGATGC- 3 ′ (seq. # 1 ) wherein only the end bases are phosphorylated is a preferred embodiment. Antisense sequences of up to 40 bases which containing this sequence may be used in accord with the teachings of this disclosure. Compositions comprising a cationic liposome of dimethyldioctadecyl ammonium bromide, phosphatidylcholine and cholesterol may be used as a carrier system. The liposomes provide a new carrier system that is particularly useful for administration of sequences for therapy.

What we claim is:  
     
         1 . A composition comprising a cationic liposome containing a cationic lipid, phosphatidylcholine and cholestrol.  
     
     
         2 . A composition of  claim 1  wherein the liposome contains an antisense oligonucleotide sequence.  
     
     
         3 . A composition of  claim 2  wherein the antisense sequence is a raf oligodeoxynucleotide.  
     
     
         4 . A composition of  claim 3  wherein the antisense sequence is of the formula 5′-GTGCTCCCATTGATGC-3′ wherein only the terminal sequences are phosphorothioated.  
     
     
         5 . A composition of  claim 1  in a pharmaceutically acceptable carrier.  
     
     
         6 . A composition of  claim 4  in a pharmaceutically acceptable carrier.  
     
     
         7 . A composition of  claim 1  wherein the pharmaceutically acceptable carrier is isotonic.  
     
     
         8 . A composition of  claim 4  wherein the pharmaceutically acceptable carrier is a buffered, isotonic solution.  
     
     
         9 . A method of radiosensitizing tumor tissue by administration of a radiosensitizing effective amount of at least one antisense oligonucleotide of no more than 40 bases containing the sequence 5′-GTGCTCCATTGATGC-3′.  
     
     
         10 . A method of  claim 9  wherein the oligonucleotide is phosphorothioated at only the end nucleotides.  
     
     
         11 . A method of  claim 9  wherein the oligonucleotide is phosphrothioated at only the end nucleotides.  
     
     
         12 . A method of  claim 9  wherein the oligonucleotide is administered intravenously.  
     
     
         13 . A method of  claim 9  wherein the oligonucleotide is administered directly to the target tissue.  
     
     
         14 . A method of  claim 9  wherein the oligonucleotide is administered into the arterial supply to the target tissue.  
     
     
         15 . A method of  claim 9  wherein the oligonucleotide is of the formula 5′-GTGCTCCATTGATGC-3′ and only the end bases only are phosphorothioted.  
     
     
         16 . A composition of matter comprising liposomes containing the sequence 5′-GTGCTCCATTGATGC-3′ in a pharmaceutically acceptable carrier.  
     
     
         17 . A composition of  claim 1  wherein the cationic lipid is dimethyldioctadecyl ammonium bromide.